Salinity-Driven Nonadditive Disruption of Digestive Energy Homeostasis in Mussels by Titanium Dioxide Nanoparticles

High Resolution Image Download MS PowerPoint Slide Titanium dioxide nanoparticles (TiO 2 NPs) are increasingly accumulating in coastal waters. Seasonal salinity fluctuations further complicate their ecological risks. We investigated how salinity modulates TiO 2 NP toxicity on digestive energy metabolism in the thick-shelled mussel Mytilus coruscus, an important coastal economic shellfish. Mussels were exposed for 14 days to three salinities (15‰, 25‰, 35‰) and two TiO 2 NP levels (0, 100 μg/L). Combined stress aggravated intestinal lesions, with significantly reduced intestinal wall thickness and increased periluminal vacuolation. Physiologically, low salinity (15‰) alone triggered an adaptive increase in succinate dehydrogenase (SDH) and cytochrome c oxidase (COX) activity ( P < 0.05). However, coexposure with TiO 2 NPs abolished this compensation. It significantly inhibited SDH, COX, and NADH dehydrogenase while increasing lactate dehydrogenase (LDH) activity. This pattern reflects a compensatory shift to anaerobic metabolism following mitochondrial dysfunction. Microbiologically, α-diversity remained unchanged, but the community structure shifted significantly. Beneficial Bacteroidetes decreased, while potential pathogens such as Vibrio and Polaribacter were enriched under low-salinity coexposure ( P < 0.05). This indicates functional dysbiosis. Transcriptomic analysis confirmed metabolic disruption. Core energy metabolism genes (glycolysis, TCA cycle) were significantly down-regulated. In contrast, antioxidant genes were up-regulated to counter oxidative stress. Collectively, these findings demonstrate that salinity and TiO 2 NPs cause complex nonadditive interaction toxicity. They disrupt energy homeostasis through a multidimensional cascade: structural injury, mitochondrial impairment, microbiome reshaping, and transcriptional reprogramming. These findings provide mechanistic insights into the interactive ecotoxicity of nanoscale pollutants. They also support ecological risk assessment in coastal waters with variable salinity.