×Island ecosystems offer unique windows into microevolutionary processes, particularly when recurrent climatic oscillations and anthropogenic pressures shape the genetic architecture of endemic taxa. This thesis investigates the population genetics, historical demography, and innate immune gene diversity of the Balearic lizard Podarcis lilfordi—an endangered lacertid lizard restricted to 43 islets across the Mallorca, Menorca, and Cabrera archipelagos—with the overarching goal of informing conservation strategies for highly fragmented insular populations. Chapter 1 explores the phylogeographic structure and genome-wide patterns of genetic diversity within the species. Using a newly assembled reference genome and >300,000 SNPs from 191 individuals across 16 islets, the analyses reveal two deeply divergent lineages corresponding to the Mallorca–Cabrera and Menorca archipelagos (mean global FST = 0.247 ± 0.09). Despite severe fragmentation, islet populations retain moderate levels of nucleotide diversity (π = 0.144 ± 0.021) and low inbreeding coefficients (FIS< 0.10), suggesting that historical connectivity, past population sizes, and possibly selection may have contributed to the retention of genetic diversity, although the precise mechanisms remain uncertain. Allelic richness increases significantly with islet surface area, indicating that larger islands may better sustain genetic diversity. Maximum-likelihood phylogenies based on concatenated SNPs support a Mallorcan origin for P. lilfordi, followed by colonization events toward Menorca and Cabrera during Pleistocene glacial lowstands, likely facilitated by temporary land connections or reduced sea barriers during periods of lowered sea levels. Chapter 2 aims at reconstructing major historical demographic events within P. lilfordi looking at three hierarchical levels: (i) within the species, (ii) within archipelagos, and (iii) within individual populations/islands, focusing on three islands under current demographic study. For this purpose, site frequency spectra models (assuming a four-year generation time and a mutation rate of 1×10⁻⁸) reveal strong population contractions during the Riss (~300–130 ka), Würm (~115–11.7 ka), and LGM (~33–19 ka), likely driven by habitat loss and climatic instability. Subsequent interglacial sea-level rises intensified fragmentation, although rare rafting events or short-lived land bridges likely permitted limited gene flow. A sharp decline in Ne around 4.3–4.5 ka coincides with early human settlement, followed by habitat transformation and predator introduction which caused the extirpation of P. lilfordi from Mallorca and Menorca by ~2 ka and severe bottlenecks on remnant islets. Chapter 3 explores the genetic potential of P. lilfordi to respond to infection threats by investigating its innate immune gene repertoire. Specifically, the chapter presents the first genome-wide characterization of AMPs in this species and compares them with close relatives in the Lacertidae family. Three AMP families were identified— beta-defensins, ovo-defensins (including three proline-rich variants), and cathelicidins—totaling 77 genes. Most beta- and ovo-defensins are located on chromosome 3, and cathelicidins on chromosome 12, flanked by conserved genomic markers. Comparative analyses revealed 58 orthologs or paralogs shared with P. muralis, P. raffonei, and Zootoca vivipara, including cathelicidins and ovo-defensins-PrAMPs, most of which were one-to-one orthologs between species, as well as recent gene expansions in beta- and ovo-defensins. Phylogenetic reconstructions suggest potential convergent evolution of AMP sequences across distantly related squamates. Despite historical bottlenecks and absence of gene flow, P. lilfordi retains high AMP gene diversity, potentially contributing to population resilience in isolated environments. In summary, this thesis demonstrates that P. lilfordi has withstood both Pleistocene climatic shifts and recent human impacts while preserving significant genetic and functional variation. The identification of distinct genetic lineages and high immunogenomic diversity highlights the importance of managing each islet population as a distinct conservation unit. These findings offer a strong genomic framework for biodiversity conservation strategies targeting this key insular species, with broader implications for all isolated vertebrate populations in dynamic island ecosystems.