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Global climate change and acquired resistance to insecticides are threats to world food security.Drosophila suzukii,a devastating invasive pest in many parts of the world,causes substantial economic losses to fruit production industries,forcing farmers to apply broad-spectrum insecticides frequently.This could lead to the development of insecticide resistance.We determined the Lethal Concentration 50 (median lethal concentration,LC50) values of zeta-cypermethrin,spinosad,and malathion insecticides against D.suzukii colonies established from Clarke and Pierce county Georgia,United States.The LC50 values were 3 fold higher in the Pierce county population for all insecticide treatments.We then used RNA sequencing to analyze the responses of Pierce and Clarke population flies surviving a LC50 treatment of the 3 insecticides.We identified a high number of differentially expressed genes that are likely involved in detoxification and reduced cuticular penetration,especially in the Pierce population,with extensive overlap in differentially expressed genes between the 3 insecticide treatments.Finally,we predicted fewer nonsynonymous single nucleotide variants having deleterious effects on protein function among detoxification,insecticide target,and cuticular protein encoding genes in Pierce flies.Thus a combination of increased gene expression and fewer deleterious single nucleotide variants highlights molecular mechanisms underlying the higher LC50 values for Pierce population flies.