I've seen some people headcanon Big Mac as a transgender mare, and I really like the idea. After re-watching some older MLP episodes, it makes sense. Big Mac seemed very comfortable wearing female clothes in Brotherhood Social and presenting as a mare. And he imagined himself as a pretty alicorn princess in Do Princesses Dream of Magic Sheep.
I like to headcanon that Big Mac always felt uncomfortable in his body, but he really had no idea how to express his gender identity. After all, with all his chores to worry about on Sweet Apple Acres, he had no time to truly reflect on it. After pretending to be Orchard Blossom for Applebloom, Big Mac really felt a connection with the alter ego. For the first time in ages, he finally felt comfortable with himself. So, he began to secretly experiment with drag, not wanting to let go of "Aunty Orchard". Not long after, Applejack discovered him donning a frilly dress and applying makeup in his room. Confessions ensued, and the whole Apple Family was incredibly supportive during the process. After that, Big Mac quickly discovered that he was transgender and started the transition.
Now, Big Mac is known as Honeycrisp Blossom, and she couldn't be happier!