Anthropogenic effect on the environment includes pollution, i.e. emission of various inorganic and organic substances into the ecosystem. The earliest effect of pollution on the organisms can be detected on the molecular and cell levels. Studies of genotoxicity biomarkers such as DNA damage are of great importance for understanding pollution related stress and environmental risk assessment. The genotoxic effect was studied on the Mytilus galloprovincialis haemocytes using comet assay. Native populations were sampled in fall 2013. and in spring 2013 on the locations: Pula - harbour, Ičići, Lim Bay, Rijeka - harbour, shipyard in the northern Adriatic, Split - harbour, Marina, Trogir - marina, Adriavinil, Zadar Borik, Zadar – marina, Gruž - harbour, Mali Ston, Ston, NP Mljet. In addition, population Marina was cage exposed on six sites in transplant experiment, and populations Gruž and Marina were exposed to copper in mesocosm experiment. The pollution effect on the mussel populations was estimated by literature data and chemical analysis of heavy metals in the mussel tissue. These results indicated low to moderate level of pollution. DNA damage analysis in native populations did not show significant difference between all of the control and polluted stations. The biggest aberration was seen in the mussels from the locations Gruž and Pula, which had the highest genotoxic effect. DNA damage analysis in transplanted populations showed slightly decreased DNA integrity in respect to the control station Marina, and statistical significance was reached only for mussels exposed at site Gruž. Mesocosm experiment showed higher DNA damage in mussels from polluted site. Seasonal fluctuations of environmental conditions at the study sites make interpretation of pollution effect complex, as seen especially in the variability of the results on DNA damage. These investigations further stress the importance of understanding the effects of natural factors (salinity, temperature, pH) for the interpretation of the data obtained. In addition, adaptation and acclimatisation of populations to local pollution may play a role in some of the response patterns observed.