Marine organisms are frequently exposed to polycyclic aromatic hydrocarbons (PAHs) which show wide-spread dispersion in the aquatic environment and varied toxicity. Among the different PAH categories, mainly pyrogenic and petrogenic PAHs have the potential to affect the health of marine ecosystem producing adverse biological effects. In this regard, there is extensive knowledge of PAH-related ecotoxic effects which include tumors, endocrine disruption (Navas and Segner, 2000) and immune-suppression (Armstrong et al., 2004). However, the toxicity of these compounds can vary, depending on the processes of uptake, metabolism and elimination (Krahn and Stein, 1998; Zhang et al., 2016). Sea turtles are particularly at risk of exposure to PAH due to the use of different habitat types in different life stages. PAH exposure appears to be from multiple routes (e.g. skin contact, inhalation, consumption of contaminated prey and sediment, direct oil ingestion, and oil fouling of both sense organs and eggs (Milton et al., 2003) and can result in a rapid uptake. Data from different studies reported that PAHs were consistently shown to be significantly elevated in plasma and tissues of sea turtles from different areas (Alam and Brim, 2000; Camacho et al., 2012; Camacho et al., 2013; Camacho et al., 2014; Casini et al., 2018), particularly the Adriatic basin (Bucchia et al., 2015; Cocci et al., 2018). The Adriatic Sea, in fact, has been identified to be particularly susceptible to pollution (Fossi et al., 2018; Magi et al., 2002; Makatounis et al., 2017; Storelli et al., 2005). However, limited data are available on the rate of uptake and possible effects of PAH exposure in juvenile and adult sea turtles as compared to other vertebrate species. Because PAHs tend to be quickly metabolized in vertebrates, such as fish and marine mammals, bioaccumulation of these compounds in turtles may be related to xenobiotic-metabolizing enzyme saturation by other contaminants (Swartz et al., 2003) or to a generally lower detoxification metabolism of reptiles as recently suggested for lizards (Chen et al., 2016). Furthermore, low molecular PAHs tend to be more bioavailable, more sensitive to UV photolysis (Korfmacher et al., 1980), less metabolizable and highly associated with genotoxic properties, the latter was also observed in turtles (Matson et al., 2005). Sea turtle exposure to PAHs can reasonably be regarded as chronic due to continuous exposure via food and the environment. Ranging from skin sloughing, histological dermal changes (Lutz, 1989), to CYP1A5 mRNA upregulation (Webb et al., 2014) and DNA fragmentation (Casini et al., 2018), the range of PAH adverse effects is wide. However, data on specific effects of PAH in sea turtles should yet be considered absolutely deficient. Before this study, we have investigated the effect of persistent organic pollutants (POPs) on gene biomarkers and DNA methylation in juvenile loggerhead sea turtles (Caretta caretta) from the northern and middle Adriatic Sea. Our results showed that increased levels of HSP60, CYP1A and ER? gene expression are positively correlated with the concentrations of specific PAH congeners (Cocci et al., 2018). Furthermore, we have demonstrated that global DNA methylation is positively associated with total PAHs, particularly LMW-PAHs. However, little is known about the specific effects of PAH-induced oxidative stress on the antioxidant pathways, DNA repair and detoxification gene transcription in marine turtle species. Therefore, the present work investigated to identify new biomarkers and the most prevalent pathways of PAH exposure in loggerhead sea turtles, using targeted detoxification and methylation genomic approach in whole blood cells.