A Review on Climate Change Redefining Tetrodotoxin Accumulation and Ecological Dynamics in Pufferfishes

Pufferfishes (Tetraodontidae) accumulate tetrodotoxin, a potent neurotoxin, primarily through microbial and trophic pathways rather than endogenous biosynthesis, linking their toxicity directly to marine microbial ecology and food-web structure. Anthropogenic climate change, ocean warming, deoxygenation, and acidification are reshaping the environmental conditions that govern TTX production, transfer, and accumulation. This review synthesizes evidence from 62 studies (28 with quantitative data) identified through a PRISMA-ScR-compliant search. We organize findings around three mechanistic pathways: (1) warming-associated proliferation of TTX-producing bacteria and consequent shifts in environmental TTX availability, (2) climate-driven range shifts and hybridization that generate novel and unpredictable toxicity phenotypes, and (3) physiological responses of pufferfishes to warming, hypoxia, and acidification that may alter toxin allocation. We identify priority research needs, long-term monitoring, multi-stressor experiments, and standardized LC-MS/MS-based surveillance and outline an integrated framework for anticipating climate-driven shifts in pufferfish toxicity.