Knowledge of genetic diversity and structure is essential for developing conservation strategies for endangered species. The advances in museum genomics can assist in better understanding the effects of over-hunting on the genome by comparing historical to present-day samples. Blue whales were hunted to the point of near extinction in the mid-twentieth century. Herein, we use whole genome sequencing to elucidate the poorly understood population structure of North Atlantic (NA) blue whales (Balaenoptera musculus musculus). We generated a de novo genome assembly of 2.49 Mbp for a NA blue whale (N50 of 1.46 Mb) to analyze 19 whole genomic sequences and 28 complete mitochondrial genomes. We included present-day and historical samples (earliest from 1900) from the Atlantic and Antarctica to understand the impact of whaling on the genetic diversity. We found low population structuring, but high genetic diversity, suggesting a single, panmictic population in the NA. We identified gene flow from fin whale to blue whales, accounting for ~3.5% of the genome. Introgression between blue and fin whales was observed in all the present-day samples but were lacking in some whales sampled early in the 20th century, which suggests increasing disruption in mate choice concomitant with decline in blue whale population. We also assembled and analyzed the transcriptome and revealed positive selection of oncogenes, which may be involved in reduced cancer rates in this largest of mammals ever known. Our sequencing and population structuring studies provide a genomic framework to guide ongoing conservation strategies for this iconic species.