Shared Mechanism, Distinct Outcomes: Transcriptomic Analysis Reveals Differential Modulation of Metabolic and Detoxification Pathways by Neonicotinoid Insecticides

Neonicotinoids are among the most widely used classes of insecticides worldwide. However, growing evidence links their exposure to metabolic disturbances, including DNA damage, endocrine disruption, and hepatic dysfunction. In this study, transcriptomic analyses were applied to investigate the gene expression changes induced by two neonicotinoids, clothianidin and thiacloprid. Our results revealed distinct treatment-driven transcriptional signatures, characterized by the upregulation of gene sets enriched in pathways associated with mitochondrial regulation, neuronal signaling, and neurodegeneration-related molecular processes, alongside the downregulation of genes involved in core metabolic processes. In addition, neonicotinoid exposure modulated gene sets associated with xenobiotic detoxification, immune response, cell proliferation, and cell adhesion. Notably, clothianidin and thiacloprid induced compound-specific transcriptional profiles, despite sharing a common mechanism of action. Furthermore, combined exposure resulted in gene expression patterns that differed from those observed with individual treatments. Together, these findings demonstrate that neonicotinoids can elicit divergent molecular responses, highlighting the importance of compound-specific toxicological assessment in non-target species.