A sunscreen UV filter disrupts energy homeostasis and impairs growth in the endangered living fossil Tachypleus tridentatus.

2-Ethylhexyl-4-methoxycinnamate (EHMC), one of the most widely used organic UV filters, is frequently detected in coastal environments, raising concerns about its effects on aquatic organisms. Here, we report that EHMC exerts multiple adverse effects on first-instar juveniles of the critically endangered tri-spine horseshoe crab (Tachypleus tridentatus). Exposure to environmentally relevant concentrations of EHMC (1, 10, and 100 μg/L) for 28 days significantly reduced body weight and carapace width, whereas short-term (7-day) exposure had no measurable effect on growth. Although ecdysone levels remained stable throughout the exposure period, altered transcription of molting-related genes and elevated activities of chitinase and β-N-acetylglucosaminidase (β-NAGase) indicated disruption of the molting process. EHMC moderately stimulated the antioxidant defense system, thereby preventing excessive oxidative damage. In addition, elevated activities of non-specific immune enzymes and upregulated transcription of immune-related genes demonstrated activation of the innate immune response. Integrated transcriptomic and lipidomic analyses revealed that lipid catabolism was enhanced to meet increased energy demands under EHMC stress, which is postulated to compensate for stress-related energy deficit and is associated with impaired molting and growth. These findings demonstrate the toxicological impacts of EHMC on T. tridentatus and provide mechanistic insights relevant to the conservation of this endangered species.