Species-specific brain transcriptomic responses to clothianidin and sulfoxaflor in pollinators

Insects that pollinate essential crops are frequently exposed to neurotoxic insecticides. Although most pollinators belong to insect lineages that diverged hundreds of millions of years ago, insecticide safety tests focus on a few model bee species. Here, we used comparative whole-brain transcriptomics to test whether sulfoxaflor and clothianidin elicit similar or distinct responses across four phylogenetically diverse pollinators: Bombus terrestris, Osmia bicornis, Lucilia sericata, and Vanessa cardui. Within each species, both insecticides produce broadly similar gene regulatory profiles, with more than 70% of differentially expressed genes shared. By contrast, transcriptional responses differed sharply across species, with no shared genes or pathways consistently disrupted. Unexpectedly, sulfoxaflor, promoted as a "bee-safe" alternative, provokes broader gene regulatory changes in non-bee species than clothianidin, a restricted neonicotinoid. Our findings reveal extensive transcriptional divergence in insecticide responses across pollinators, suggesting that risk assessments would benefit from greater phylogenetic diversity and novel molecular approaches.