Lambda-cyhalothrin disrupts ion homeostasis and triggers endoplasmic reticulum stress in first-instar Tachypleus tridentatus: An integrated physiological-transcriptomic analysis.

Residual contamination of the type II pyrethroid lambda-cyhalothrin (LCT) is documented in coastal environments, posing potential risks to benthic fauna such as Tachypleus tridentatus. We integrated acute toxicity bioassays, histopathology, Na+/K+-ATPase and Ca2+-ATPase activity assays, and transcriptomic profiling to evaluate LCT-induced effects and mechanisms in first-instar larvae. The 48-h LC50 was 41.99 μg/L. Exposed larvae displayed characteristic neurotoxicity, including motor inhibition and sustained contraction of limbs and gills. Enzyme assays showed rapid and persistent suppression of Na+/K+-ATPase and a biphasic Ca2+-ATPase response (early elevation followed by suppression), consistent with disruption of Na+-Ca2+ exchange-coupled homeostasis. RNA-seq identified 975 differentially expressed genes enriched in endoplasmic reticulum (ER) stress/unfolded protein response (UPR), redox regulation, immunity, and signaling pathways (e.g., Wnt, FoxO). Expression patterns (downregulation of BiP, HSP40, HSP90; upregulation of HSP70 isoforms, Jun-like factors, and phospholipase A2 isoforms) are consistent with ER dysfunction and secondary oxidative and immune stress. Collectively, these findings elucidate a toxicological cascade wherein LCT-induced VGSC perturbation precipitates ionoregulatory failure and subsequent ER stress/UPR activation, driving neuromuscular collapse. Beyond establishing toxicity benchmarks, the identified ATPase inhibition patterns and ER stress signatures provide specific mechanistic biomarkers for ecological risk assessment of pyrethroid exposure in benthic environments.