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Cotton (Gossypium hirsutum) is an important fiber crop worldwide. Insect attack causes cotton yield and quality losses. However, little is known about the mechanism of cotton response to insect attack. We simulated insect feeding by applying insect oral secretions (OS) to wounds, and combined transcriptome and metabolome analysis to investigate how OS from two major pest species (Helicoverpa armigera and Spodoptera litura) affect cotton defense responses. We found that respectively 12,668 and 13,379 genes were differentially expressed in comparison with wounding alone. On addition of OS, the jasmonic acid signaling pathway was rapidly and strongly induced, whereas genes involved in salicylic acid biosynthesis were downregulated. On constructing a coexpression gene network, we identified a hub gene encoding a leucine-rich repeat receptor kinase that may play an important role in early signal …