Marine ecosystems face increasing threats from chemical pollutants, particularly metals, which persist in the environment, bioaccumulate, and pose risks to marine organisms and human health. In Victoria, Australia, Burrunan dolphins (Tursiops australis), a critically endangered and endemic species, are particularly vulnerable due to their strong site fidelity to coastal regions like Port Phillip Bay and Gippsland Lakes—areas subject to significant urban, agricultural, and industrial runoff. These regions are among the most mercury (Hg)-polluted globally, with previous studies reporting elevated Hg levels in deceased dolphins. Despite this, the biological effects of metal exposure in live individuals remain poorly understood. Investigating molecular responses—especially gene expression—offers valuable insight into physiological stress and potential health impacts. This study aimed to assess metal accumulation in Burrunan dolphins and its potential effects on molecular pathways associated with detoxification, antioxidant defenses, immune function, and oxidative stress. Skin biopsies were collected from free-ranging dolphins using minimally invasive methods. Samples were preserved in RNAlater and stored at –80 °C for RNA extraction and subsequent quantitative real-time PCR (qPCR) analysis. Simultaneously, metal concentrations in the same samples were quantified using inductively coupled plasma mass spectrometry (ICP-MS). Results revealed significant associations between the expression of stress-related genes and specific metal levels, highlighting the potential use of these genes as molecular biomarkers for biomonitoring efforts. These findings emphasize the urgent need to reduce pollutant exposure in critical habitats and demonstrate the utility of molecular tools in marine conservation. By linking environmental contamination to sub-lethal molecular effects, this research supports targeted conservation strategies for Tursiops australis and provides a framework for assessing pollution impacts in marine mammals.