In the present study, we report the transcriptomic changes in Gossypium hirsutum L. leaf, in response to two sap-sucking insects (aphid and whitefly). Cotton plants were infested by these two insects, and transcriptome sequencing at an average 4.4X coverage was completed for the control and infested leaf samples. We observed that plants respond to whiteflies quickly by changing their transcriptome; whereas in case of aphids, the response is slow (Figure 1). The number of down-regulated genes that were more than the up-regulated genes in infestation by both aphids and whiteflies support the previous report which showed that aphids stimulate the suppression of more genes than does induction . Our study suggested that aphids and whiteflies influence the expression of cell and cell wall metabolism by changing the expression of enzymes of sugar metabolism such as phosphoenolpyruvate carboxylase 3, sugar translocator/posphate translocator, cell wall modifier β-Xylosidase 1, inositol oxygenase and cellulose synthase 1(Table 3). We also identified that amino acid metabolism was significantly altered by changing the transcription of key enzymes such as threonin aldolase and 4-hydroxyphenylpyruvate dioxygenase (Table 3). These insects reroute the amino acid transportation , and cotton plants probably respond to it by the suppression of the amino acid trans membrane transporter, as a defense strategy that is deployed by plants in response to infestation by aphids. In case of sap-sucking insects, the amino acid composition of plant sap determines the attractiveness of insects , and sap-sucking insects, thus, become the secondary sink of amino acid for plants and increase the genes related to the amino acid biosynthesis pathway . It was also reported earlier in A. thaliana that amino acid permease AAP6 mutant reduces the amino acid level in phloem sap and this correlated with the aphid behavior . The infestation mediates the up-regulation of senescence in response to aphids and indicates the breakdown of leaf proteins and probably the translocation of the free amino acid pool, thus forming the phloem sap . The result of cotton transcriptome in response to infestation by aphids and whiteflies showed significantly enrichment of the amino acid biosynthesis pathway (Table 5). During infestation, these insects damage the sieve tube; in response to this damage, plant respond by the release of Ca2+, which causes plugging of the sieve plate  and prevents the loss of phloem sap. However, aphids overcome this defense by secreting Ca2+-binding protein through their saliva, thus preventing clogging. In our experiment, suppression of the Ca2+-binding protein was noticed, and this may be considered an insect-influenced plant strategy for increasing the Ca2+ level in phloem sap by suppressing these genes (Additional file 9). In qualitative terms, the impact of 2-h infestations by aphids was similar to 24-h infestations by whiteflies; like cytokinin, fungus, bacteria, viruses, JA, gibberellin, and cytokinin responsive transcripts were similarly induced or suppressed by both conditions (Figure 2A and B). Further, we have screened the pathogenic organism that also influenced the expression of these insect (aphid and whitefly) infestation-responsive transcripts with the help of Genvestigator (Additional file 11). Among them, fungi such as Alternaria brassicicola, Botrytis cinerea, Blumeria graminis, Erysiphe cichoracearum, E. orontii, Golovinomyces cichoracearum, Phytophthora infestans, and P. paraistica; bacteria such as Escherichia coli and Pseudomonas syringae; and viruses such as cabbage leaf curl virus (CalCUV) and turnip mosaic virus (TuMV) were found. In contrast to chewing insects, weak wounds were created by these phloem feeders. The art-of-style insertion of these insects may be comparable to the fungus haustoria and bacterial infection response. It was reported earlier that intercellular fungal hyphae growth resembles with that of style penetration of whiteflies . The GO annotation of the differentially expressed genes for A2, A24, W2, and W24 showed the involvement of various metabolic and cellular processes (Additional file 8) during infestation by these insects. The transcriptomic reprogramming in response to infestation by aphids and whiteflies showed the up-regulation of several genes belonging to stress, response to signals and pathogens (Additional file 8). Some of the interesting features include the differential expression of transporters in response to sap-sucking insect infestation (Additional file 8); some of transporter-related transcripts are up-regulated in W2, whereas they are down-regulated in A2. The inducibility of water transporter , gluatathion S conjugate transporter , and sugar transporter  was also reported earlier in response to infestation by aphids. In W2, the genes related to various developmental processes such as seed development, post-embryonic development, multicellular development, and root development were found to be induced (Additional file 13). The relationship between developmental genes and biotic stress was reported earlier; for example, seed development genes were found to be induced in response to nematode infestation . The transcripts belonging to secondary metabolic processes such as phenyl propanoid biosynthesis, flavanoids, and aromatic compounds (Additional file 8) were up-regulated during the later phase of infestation by aphids, and these aromatic compounds may be involved in the attraction of parasitoid of aphids . The transcripts of some of the hydrolyses and carboxylesterase were enriched in 2 h of infestation with aphids (Additional file 8). The differential expression of hydrolase and transferase in response to biotic and abiotic stress was shown in the form of the differential expression of glycosyl hydrolase family 1 in P. rapae infestation in Brassica oleracea  and UDP-glycosyltransferase activity in toxic detoxification during insect infestation . The hydrolysis of the product of glucosinolate gives the cyanides and nitriles, which are toxic to herbivores, and the transportation of these to the phloem leads to the deterrence of herbivorous and phloem-feeding insects. The role of glucosinolates in plant defense is well reported; they form in plant tissue and are transported to the site of insect attack . In our result, enzyme benzoate-CoA ligase, which is involved in benzoyloxyglucosinolate synthesis, and genes such as nitrate transporter 1.9 and transporter protein containing the properties of transporters of glucosinolate  (Additional file 13) were differentially expressed in response to sap-sucking insect infestation. Similarly, the induction of glutathione S-transferases members in response to cabbage aphids , cell wall modification enzymes pectin transferase  was reported earlier. The sap-sucking insects are the chief mediators or vectors of spreading plant viruses. There is a decrease in the expression of Poly (A) binding protein 2 (PABP2) in both insect-infested leaves, which help in the transmission of sap-sucking, insect-mediated virus infection and the translation of viral RNA molecule , heat shock protein 70 , and chloroplast RNA-binding protein 29, which are used in viral protein folding (Additional file 13). Salicylic acid (SA), jasmonic acid (JA), and ethylene signaling pathways are involved in the regulation of plant-induced defense after attacks by pathogens and insects . The JA-responsive pathway is usually activated when there is an attack by necrotrophic and chewing insects; whereas the SA mediates the defense response against biotrophic pathogens and insects such as aphids and whiteflies . Aphids and whiteflies influenced the expression of cotton JA and ET synthesis genes in our experiment. The role of JAR1 in JA-mediated defense development has been already reported. Further, the constitutive expression of JA- and ET-signaling pathways in CEV1 (Constitutive expression of VSP 1) mutant of Arabidopsis, which was resistant to aphid growth, was reported . We identified that at a later phase, the infestation of whiteflies leads to the suppression of CEV1 expression (Additional file 4). Thus, our results indicate the fine tuning of the JA pathway in cotton in response to the infestation by aphids and whiteflies. Further, in addition to changes in the expression of the genes involved in JA and ET biosynthesis, we also identified that the expression of hormonal signaling kinases, including MAP2K9 and MAPK6, was also altered, and the relation of MAP kinases in defense mechanisms involving JA, SA, and ET is well established . We also identified that the expression of enzymes involved in oxidative radical scavenging were suppressed after the infestation by aphid and whiteflies (Table 4); these may lead to an increase in oxidative radicals and H2O2 in the phloem sap, which is a probable strategy that is deployed by cotton plants against insect infestation . We also report the involvement of ABA and GA pathways during the infestation by aphids and whiteflies in cotton (Figure 2A). The role of ABA [64, 65] and GA  in plant–insect interaction has been recently shown. Further, the involvement of ABA and GA during the defense responses against green bug phloem feeding in sorghum  has been recently demonstrated. It has been reported that the increase in GA causes the increase in trichome density, and this may protect the plants from aphids and whiteflies . Our results further showed the involvement of cytokinin in defense responses to aphids and especially whiteflies (Figure 2A). The involvement of cytokinins in defense responses toward aphids or whiteflies has not been reported earlier; however, the role of cytokinins in plants and bacterial interactions  and bacterial isopentenyl transferase (ipt) genes, which are involved in cytokinin biosynthesis, which, in turn, are involved in resistance to the tobacco hornworm and green peach aphid nymphs, was reported . The down-regulation of genes such as overexpressors of cationic peroxidase 3- OCP3 (Additional file 9 and Additional file 10B), non-specific lipase , LOX1 , and TGA2  which leads to the suppression of phytohormonal-mediated plant resistance and increase in the expression of DMR6 (Additional file 4 and Additional file 10A), which is a positive regulator of the susceptibility of plants to pathogens , showed insect-mediated suppression of plant defense and compatible infestation of these insects. Plants assimilate heavy metals such as Ni , Zn , and Se  for protection against herbivorous insects. We identified the enrichment of selenometallo metabolism in the case of whiteflies infested both cotton and Arabidopsis plant (Figure 4D). Selenium is a member of sulfur(s) group, and, hence, plants readily assimilate selenate in place of sulfur into cysteine as selenocysteine (SeCys) via the sulfur metabolic pathway ; this explains the enrichment of the sellanometallo metabolic pathway in response to whiteflies. We also observed the enrichment of the transcript related to RNA transport both in cotton and Arabidopsis plants during aphid infestation (Figure 3C). It is already reported that viruses hijack the plant RNA transportation system for disease spreading. In parellal, plant activate the pathway of mRNA surveillance to control formation of aberrant RNA, which is a defense mechanism, was also generated in response to virus infection in plants . Sap-sucking insects are potential vectors for plant-borne viruses ; thus, our result also proposes an interesting question as to whether plants understand the potential threat of virus infection after the infestation by aphids and whiteflies.