Metabolomics for Understanding Heavy Metal Stress Responses in MarineOrganisms: A Comprehensive Review

Abstract: Heavy metal pollution from anthropogenic activities poses a threat to marine ecosystems, causing complex, often sub-lethal biochemical disturbances in aquatic organisms. Studies using traditional toxicological assessments mainly offer limited insight into the underlying mechanisms of metal- induced stress. While metabolomics, in particular Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) based studies, has emerged as an important tool in investigating organism-level responses at a systems biology level. This review has made effort in compiling current metabolomic research on the impacts of heavy metals, that includes cadmium (Cd), mercury (Hg), copper (Cu), zinc (Zn), arsenic (As), and silver (Ag), on marine model organisms such as the Manila clam (Ruditapes philippinarum), green mussel (Perna viridis), Mediterranean mussel (Mytilus galloprovincialis), oyster (Crassostrea hongkongensis), various fish species, and crustaceans. It is observed that there are consistent metabolic disruptions in pathways related to energy metabolism (e.g., ATP, succinate), osmoregulation (e.g., taurine, betaine), and amino acid balance (e.g., branched-chain amino acids, glutamate). The metabolic responses were mainly tissue-specific and depended on life stage and environmental variables, such as salinity or co-exposure to other pollutants. Altogether, metabolomics provides sensitive, early biomarkers of heavy metal stress. This can contribute to a deeper understanding of ecological risk assessment and to develop more effective marine conservation strategies.