Understanding the genomic consequences of population decline is a dynamic challenge in evolutionary biology and conservation. Declining population sizes can lead to reduced heterozygosity and elevated frequency of deleterious alleles, resulting in inbreeding depression, increased susceptibility to diseases, and reduced adaptive capacity. However, empirical research, especially in populations with ongoing gene flow, remains scarce. To investigate these dynamics, I integrate ecological data, whole-genome sequences (WGS), and population genetics and metagenomic approaches for multiple populations encompassing the entire spectrum of population size and demographic trajectories in the Florida Scrub-Jay (FSJ; Aphelocoma coerulescens).First, I investigate two subpopulations with contrasting demographic trajectories within the same metapopulation. Using BeadChip SNPs and demographic data for 288 FSJ sampled in 2000 and 2008, I show that in just a few generations after the onset of residential development, the declining population already exhibited lower site-based heterozygosity, higher levels of inbreeding, and increased relatedness compared to the intact population within a managed, biological preserve. This study emphasizes the importance of conservation intervention even in the early stages of a bottleneck. Expanding on this work, I use deep-coverage WGS for 241 individuals, sampled in the early 1990s and in 2017 from five focal populations to characterize in detail the impacts of varying population size and genetic isolation across the entire species. I also implement genome-wide and haplotype-based methods to show how historic and recent demographic histories have shaped current patterns of genetic variation in FSJ. This study highlights the complex interplay between effective population size and gene flow in mediating levels of genetic diversity and inbreeding. Finally, under the assumption that blood is sterile except in the case of pathogenic infections, I assess the potential impacts of reduced heterozygosity in 291 FSJ hosts on their blood-microbiome using a metagenomics approach. Contrary to expectations, I show a negative correlation between blood-microbial diversity and host inbreeding. Nonetheless, this study underscores the importance of microbiome research in conservation genetics and joins the mounting body of literature challenging the conventionally held belief of a sterile blood environment in healthy individuals.