Deltamethrin Selection Drives Transcriptomic Changes in Detoxification, Immune, and Cuticle Genes in Aedes aegypti

The rapid global expansion of <i>Aedes aegypti</i>-borne diseases such as dengue, chikungunya, and Zika has positioned this mosquito as a key target for vector control programs. These programs rely heavily on insecticide use, leading to the widespread emergence of insecticide resistance. Understanding the molecular basis of resistance is essential for developing effective management strategies. In this study, we employed a whole-transcriptome (RNA-seq) approach to analyze gene expression in three <i>Ae. aegypti</i> populations from Mexico that underwent four generations of laboratory selection with deltamethrin. Several cytochrome P450 genes (CYP6AG4, CYP6M5, CYP307A1) and a chitin-binding peritrophin-like gene (Ae-Aper50) were significantly overexpressed following selection, supporting roles for both detoxification and midgut protection. We also observed a consistent downregulation of cuticular protein genes in deltamethrin-selected groups relative to the baseline populations, suggesting their involvement in baseline tolerance rather than induced resistance. Additionally, the overexpression of immune- and stress-related genes, including the RNA helicase MOV-10, indicates that insecticide selection may trigger broader physiological responses. These findings highlight complex, multi-pathway transcriptomic changes associated with resistance development in <i>Ae. aegypti</i>.